Oral Anti-Diabetic Agents-Review and Updates

Abstract

Diabetes is a chronic metabolic disorder with high mortality rate and with defects in multiple biological systems. Two major types of diabetes are recognized, type 1 and 2 with type 2 diabetes (T2D) being by far the more prevalent type. As diabetes affects multiple biological functions, the use of multiple drug classes having different mode of actions is required in order to optimize therapy in diabetic patients. Five major classes of oral antidiabetic agents (OHA) have traditionally been used for the management of patients with T2D. These include the sulphonylureas, meglitinides, biguanides, thiazolidinediones and the alpha-glucosidase inhibitors. Several newer classes of agents have also been introduced recently in the pharmacotherapy of T2D, including the incretin mimetics, the dipeptidy peptidase 4 (DPP-4) inhibitors, the sodium glucose co-transporter 2 (SGLT 2) inhibitors and more recently, the dual peroxisome proliferator-activated receptor (PPAR) agonists. Each of these agents has been shown in various experimental and clinical settings to be efficacious in T2D, but each is also associated with a number of adverse effects. Despite the vast array of drugs introduced, metformin, a biguanide, largely remains the first choice mono therapy in T2D patients but several combination options are also available in poly pharmacy when mono therapy fails to produce the required glycemic control. The increasing number of drugs, together with numerous combination options in poly pharmacy, presents with the clinician an increasing complexity of therapeutic options. The likely pathogenetic mechanism of diabetes operating in the patient, as well as the mode of action, efficacy and safety of the drugs are some of the major considerations in the choice of any given agent or its combinations. This review therefore focuses on the mode of action, pharmacokinetics, indications, efficacy and adverse effects of the OHA used in T2D.